tbuckley/cabot-search huggingface dataset:
Prednisone vs Placebo and Live Birth in Patients With Recurrent Implantation Failure Undergoing In Vitro Fertilization
Authors: Yun Sun, Linlin Cui, Yao Lu, Jichun Tan, Xi Dong, Tianxiang Ni, Junhao Yan, Yichun Guan, Guimin Hao, Jia-Yin Liu, Bo Zhang, Daimin Wei, Yan Hong, Yaqiong He, Jia Qi, Bing Xu, Juanjuan Lu, Qian Zhang, Shanshan Zhao, Xiaowei Ji, Xiaofang Du, Jie Zhang, Jinyong Liu, Jing Wang, Yingqin Huang, Dongmei Huang, Yanzhi Du, Hugo Vankelecom, Heping Zhang, Zi-jiang Chen
Journal: JAMA (2023)

Implantation failure remains a critical barrier to in vitro fertilization. Prednisone, as an immune-regulatory agent, is widely used to improve the probability of implantation and pregnancy, although the evidence for efficacy is inadequate.To determine the efficacy of 10 mg of prednisone compared with placebo on live birth among women with recurrent implantation failure.A double-blind, placebo-controlled, randomized clinical trial conducted at 8 fertility centers in China. Eligible women who had a history of 2 or more unsuccessful embryo transfer cycles, were younger than 38 years when oocytes were retrieved, and were planning to undergo frozen-thawed embryo transfer with the availability of good-quality embryos were enrolled from November 2018 to August 2020 (final follow-up August 2021).Participants were randomized (1:1) to receive oral pills containing either 10 mg of prednisone (n = 357) or matching placebo (n = 358) once daily, from the day at which they started endometrial preparation for frozen-thawed embryo transfer through early pregnancy.The primary outcome was live birth, defined as the delivery of any number of neonates born at 28 or more weeks' gestation with signs of life.Among 715 women randomized (mean age, 32 years), 714 (99.9%) had data available on live birth outcomes and were included in the primary analysis. Live birth occurred among 37.8% of women (135 of 357) in the prednisone group vs 38.8% of women (139 of 358) in the placebo group (absolute difference, -1.0% [95% CI, -8.1% to 6.1%]; relative ratio [RR], 0.97 [95% CI, 0.81 to 1.17]; P = .78). The rates of biochemical pregnancy loss were 17.3% in the prednisone group and 9.9% in the placebo group (absolute difference, 7.5% [95% CI, 0.6% to 14.3%]; RR, 1.75 [95% CI, 1.03 to 2.99]; P = .04). Of those in the prednisone group, preterm delivery occurred among 11.8% and of those in the placebo group, 5.5% of pregnancies (absolute difference, 6.3% [95% CI, 0.2% to 12.4%]; RR, 2.14 [95% CI, 1.00 to 4.58]; P = .04). There were no statistically significant between-group differences in the rates of biochemical pregnancy, clinical pregnancy, implantation, neonatal complications, congenital anomalies, other adverse events, or mean birthweights.Among patients with recurrent implantation failure, treatment with prednisone did not improve live birth rate compared with placebo. Data suggested that the use of prednisone may increase the risk of preterm delivery and biochemical pregnancy loss. Our results challenge the value of prednisone use in clinical practice for the treatment of recurrent implantation failure.Chinese Clinical Trial Registry Identifier: ChiCTR1800018783.
Remifentanil vs Neuromuscular Blockers During Rapid Sequence Intubation Among Patients at Risk of Aspiration
Authors: Boris Mraovic, Noah J. Timko, Tatjana Simurina
Journal: JAMA (2023)

To the Editor Although we agree with the conclusion that use of remifentanil is inferior to neuromuscular blocking agents, we have some concerns about the recent study1 that examined whether patients at risk of aspiration could safely undergo intubation without use of neuromuscular blocking agents.
Developing an Evolutionary Baseline Model for Humans: Jointly Inferring Purifying Selection with Population History
Authors: Parul Johri, Susanne P Pfeifer, Jeffrey D Jensen
Journal: Molecular Biology and Evolution (2023)

Abstract Building evolutionarily appropriate baseline models for natural populations is not only important for answering fundamental questions in population genetics—including quantifying the relative contributions of adaptive versus nonadaptive processes—but also essential for identifying candidate loci experiencing relatively rare and episodic forms of selection (e.g., positive or balancing selection). Here, a baseline model was developed for a human population of West African ancestry, the Yoruba, comprising processes constantly operating on the genome (i.e., purifying and background selection, population size changes, recombination rate heterogeneity, and gene conversion). Specifically, to perform joint inference of selective effects with demography, an approximate Bayesian approach was employed that utilizes the decay of background selection effects around functional elements, taking into account genomic architecture. This approach inferred a recent 6-fold population growth together with a distribution of fitness effects that is skewed towards effectively neutral mutations. Importantly, these results further suggest that, although strong and/or frequent recurrent positive selection is inconsistent with observed data, weak to moderate positive selection is consistent but unidentifiable if rare.
Image-guided Bronchoscopy: Established and Emerging Approaches
Authors: Kai E. Swenson, Emily A. DuComb, David Abia-Trujillo, Adnan Majid, Mihir S. Parikh
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"Image-guided Bronchoscopy: Established and Emerging Approaches." American Journal of Respiratory and Critical Care Medicine, 208(1), pp. 98–100
25‐hydroxyvitamin D and risk of atopic diseases and infections in early childhood
Authors: Nicklas Brustad, Min Kim, Frederikke Skov, Ann‐Marie Schoos, Jakob Stokholm, Klaus Bønnelykke, Bo L. Chawes
Journal: Allergy (2023)

Appendix S1: Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Interlink between the gut microbiota and inflammation in the context of oxidative stress in Alzheimer’s disease progression
Authors: Tushar K. Das, Bhanu P. Ganesh
Journal: Gut Microbes (2023)

The microbiota-gut-brain axis is an important pathway of communication and may dynamically contribute to Alzheimer's disease (AD) pathogenesis. Pathological commensal gut microbiota alterations, termed as dysbiosis, can influence intestinal permeability and break the blood-brain barrier which may trigger AD pathogenesis via redox signaling, neuronal, immune, and metabolic pathways. Dysbiosis increases the oxidative stress. Oxidants affect the innate immune system through recognizing microbial-derived pathogens by Toll-like receptors and initiating the inflammatory process. Most of the gut microbiome research work highlights the relationship between the gut microbiota and AD, but the contributory connection between precise bacteria and brain dysfunction in AD pathology cannot be fully demonstrated. Here, we summarize the current information of the fundamental connections between oxidative stress, inflammation, and gut dysbiosis in AD. This review emphasizes on the involvement of gut microbiota in the regulation of oxidative stress, inflammation, immune responses including central and peripheral cross-talk. It provides insights for novel preventative and therapeutic approaches in AD.
Assessment of Tumor Mutational Burden and Outcomes in Patients With Diverse Advanced Cancers Treated With Immunotherapy
Authors: Charu Aggarwal, Rotem Ben-Shachar, Yinjie Gao, Seung Won Hyun, Zachary Rivers, Carrie Epstein, Kristiyana Kaneva, Chithra Sangli, Halla Nimeiri, Jyoti Patel
Journal: JAMA Network Open (2023)

Importance There are few studies assessing the association of tumor mutational burden (TMB) and clinical outcomes in a large cohort of patients with diverse advanced cancers. Objective To clinically validate a TMB biomarker from a next-generation sequencing targeted gene panel assay. Design, Setting, and Participants A prespecified cohort study using the deidentified clinicogenomic Tempus database of patients sequenced between 2018 and 2022, which contained retrospective, observational data originating from 300 cancer sites including 199 community sites and 101 academic sites. Patients with advanced solid tumors across 8 cancer types and more than 20 histologies, sequenced with Tempus xT who were treated with immune checkpoint inhibitors (ICIs) in the first-line or second-line setting were included. Data were analyzed from September 2018 to August 2022. Exposure Treatment with US Food and Drug Administration (FDA)–approved antiprogrammed cell death-1/programmed cell death-ligand 1 (PD-1/PD-L1) ICI and/or in combination with a cytotoxic T-lymphocyte-associated protein-4 ICI. Main Outcomes and Measures The primary outcome was the association of tumor mutational burden (TMB) binary category (high [≥10 mut/mb] vs low) with overall survival (OS) in patients treated with ICIs. Secondary outcomes were progression-free survival (PFS), and time to progression (TTP). Results In the evaluable cohort of 674 patients, the median (IQR) age was 69.4 (28.6-89.8) years, 271 patients (40.2%) were female, and 435 patients (64.5%) were White. The most common advanced cancers were non–small cell lung cancer (330 patients [49.0%]), followed by bladder cancer (148 patients [22.0%]), and head and neck squamous cell carcinoma (96 patients [14.8%]). Median (IQR) follow-up was 7.2 (3.2-14.1) months. High TMB (TMB-H) cancers (206 patients [30.6%]) were significantly associated with longer OS than low TMB (TMB-L) cancers (hazard ratio [HR], 0.72; upper confidence bound [UCB], 0.91; P = .01). In a prospective subset of 403 patients treated with ICIs after TMB testing, TMB-H cancers (135 patients [33.5%]) were significantly associated with longer OS (HR, 0.61; UCB, 0.84; P = .005), PFS (HR, 0.62; UCB, 0.82; P = .003), and TTP (HR, 0.67; UCB, 0.92; P = .02) than TMB-L cancers. An overall survival benefit was seen regardless of the type of ICI used (pembrolizumab, 339 patients; HR, 0.67; UCB, 0.94; P = .03), other ICIs (64 patients; HR, 0.37; UCB, 0.85; P = .03), and after adjusting for PD-L1 and microsatellite stability status (403 patients; HR = 0.67; UCB, 0.92; P = .02). Conclusions and Relevance In this cohort study of patients with advanced solid tumors treated with ICIs in diverse clinics, TMB-H cancers were significantly associated with improved clinical outcomes compared with TMB-L cancers.
Focused ultrasound enhances transgene expression of intranasal hGDNF DNA nanoparticles in the sonicated brain regions
Authors: Amirah E.-E. Aly, Tao Sun, Yongzhi Zhang, Zejun Li, Margee Kyada, Qingxi Ma, Linas Padegimas, Ozge Sesenoglu-Laird, Mark J. Cooper, Nathan J. McDannold, Barbara L. Waszczak
Journal: Journal of Controlled Release (2023)

The therapeutic potential of many gene therapies is limited by their inability to cross the blood brain barrier (BBB). While intranasal administration of plasmid DNA nanoparticles (NPs) offers a non-invasive approach to bypass the BBB, it is not targeted to disease-relevant brain regions. Here, our goal was to determine whether focused ultrasound (FUS) can enrich intranasal delivery of our plasmid DNA NPs to target deeper brain regions, in this case the regions most affected in Parkinson's disease. Combining FUS with intranasal administration resulted in enhanced delivery of DNA NPs to the rodent brain, by recruitment and transfection of microglia. FUS increased transgene expression by over 3-fold after intranasal administration compared to intravenous administration. Additionally, FUS with intranasal delivery increased transgene expression in the sonicated hemisphere by over 80%, altered cellular transfection patterns at the sonication sites, and improved penetration of plasmid NPs into the brain parenchyma (with a 1-fold and 3-fold increase in proximity of transgene expression to neurons in the forebrain and midbrain respectively, and a 40% increase in proximity of transgene expression to dopaminergic neurons in the substantia nigra). These results provide evidence in support of using FUS to improve transgene expression after intranasal delivery of non-viral gene therapies.
Development of a Novel DNA Aptamer Targeting Colorectal Cancer Cell‐Derived Small Extracellular Vesicles as a Potential Diagnostic and Therapeutic Agent
Authors: Byung Seok Cha, Young Jun Jang, Eun Sung Lee, Do Yeon Kim, Ji Su Woo, Jinseo Son, Seokjoon Kim, Jiye Shin, Jinjoo Han, Seokhwan Kim, Ki Soo Park
Journal: Advanced Healthcare Materials (2023)

Colorectal cancer (CRC) as the second leading cause of global cancer deaths poses critical challenges in clinical settings. Cancer-derived small extracellular vesicles (sEVs), which are secreted by cancer cells, have been shown to mediate tumor development, invasion, and even metastasis, and have thus received increasing attention for the development of cancer diagnostic or therapeutic platforms. In the present study, the sEV-targeted systematic evolution of ligands by exponential enrichment (E-SELEX) is developed to generate a high-quality aptamer (CCE-10F) that recognizes and binds to CRC-derived sEVs. Via an in-depth investigation, it is confirmed that this novel aptamer possesses high affinity (Kd = 3.41 nm) for CRC-derived sEVs and exhibits a wide linear range (2.0 × 104 -1.0 × 106 particles µL-1 ) with a limit of detection (LOD) of 1.0 × 103 particles µL-1 . Furthermore, the aptamer discriminates CRC cell-derived sEVs from those derived from normal colon cell, human serum, and other cancer cells, showing high specificity for CRC cell-derived sEVs and significantly suppresses the critical processes of metastasis, including cellular migration, invasion, and angiogenesis, which are originally induced by sEVs themselves. These findings are highly encouraging for the potential use of the aptamer in sEV-based diagnostic and therapeutic applications.
<i>BRCA2</i> Germline Mutations Identify Gastric Cancers Responsive to PARP Inhibitors
Authors: Annalisa Petrelli, Sabrina Rizzolio, Filippo Pietrantonio, Sara E. Bellomo, Matteo Benelli, Loris De Cecco, Dario Romagnoli, Enrico Berrino, Claudia Orrù, Salvatore Ribisi, Daniel Moya-Rull, Cristina Migliore, Daniela Conticelli, Irene M. Maina, Elisabetta Puliga, Violeta Serra, Benedetta Pellegrino, Alba Llop-Guevara, Antonino Musolino, Salvatore Siena, Andrea Sartore-Bianchi, Michele Prisciandaro, Federica Morano, Maria Antista, Uberto Fumagalli, Giovanni De Manzoni, Maurizio Degiuli, Gian Luca Baiocchi, Marco F. Amisano, Alessandro Ferrero, Caterina Marchiò, Simona Corso, Silvia Giordano
Journal: Cancer Research (2023)

Abstract Despite negative results of clinical trials conducted on the overall population of patients with gastric cancer, PARP inhibitor (PARPi) therapeutic strategy still might represent a window of opportunity for a subpopulation of patients with gastric cancer. An estimated 7% to 12% of gastric cancers exhibit a mutational signature associated with homologous recombination (HR) failure, suggesting that these patients could potentially benefit from PARPis. To analyze responsiveness of gastric cancer to PARPi, we exploited a gastroesophageal adenocarcinoma (GEA) platform of patient-derived xenografts (PDX) and PDX-derived primary cells and selected 10 PDXs with loss-of-function mutations in HR pathway genes. Cell viability assays and preclinical trials showed that olaparib treatment was effective in PDXs harboring BRCA2 germline mutations and somatic inactivation of the second allele. Olaparib responsive tumors were sensitive to oxaliplatin as well. Evaluation of HR deficiency (HRD) and mutational signatures efficiently stratified responder and nonresponder PDXs. A retrospective analysis on 57 patients with GEA showed that BRCA2 inactivating variants were associated with longer progression-free survival upon platinum-based regimens. Five of 7 patients with BRCA2 germline mutations carried the p.K3326* variant, classified as “benign.” However, familial history of cancer, the absence of RAD51 foci in tumor cells, and a high HRD score suggest a deleterious effect of this mutation in gastric cancer. In conclusion, PARPis could represent an effective therapeutic option for BRCA2-mutated and/or high HRD score patients with GEA, including patients with familial intestinal gastric cancer. Significance: PARP inhibition is a potential strategy for treating patients with gastric cancer with mutated BRCA2 or homologous repair deficiency, including patients with familial intestinal gastric cancer, for whom BRCA2 germline testing should be recommended.
Screening for Latent Tuberculosis Infection Among Non–US-Born Adults in the US
Authors: Priya B. Shete, Amy S. Tang, Jennifer Flood
Journal: JAMA (2023)

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Availability, Cost, and Consumer Ratings of Popular Nonvalidated vs Validated Blood Pressure–Measuring Devices Sold Online in 10 Countries
Authors: Dean S. Picone, Niamh Chapman, Martin G. Schultz, Aletta E. Schutte, George S. Stergiou, Paul K. Whelton, James E. Sharman
Journal: JAMA (2023)

This study examines the availability, cost, and consumer ratings of blood pressure–measuring devices relative to validation status across 10 countries.
Remifentanil vs Neuromuscular Blockers During Rapid Sequence Intubation Among Patients at Risk of Aspiration—Reply
Authors: Nicolas Grillot, Antoine Roquilly
Journal: JAMA (2023)

In Reply We appreciate these Letters about our study,1 which failed to demonstrate the noninferiority of remifentanil compared with neuromuscular blockers on rates of successful intubation on the first attempt without major complications in patients at risk of aspiration.
Costimulatory domains direct distinct fates of CAR-driven T cell dysfunction
Authors: Mehmet Emrah Selli, Jack Landmann, Marina Terekhova, John Lattin, Amanda Heard, Yu-Sung Hsu, Tien-Ching Chang, Ju-fang Chang, John M Warrington, Helen Ha, Natalie L Kingston, Graham Hogg, Michael Slade, Melissa M Berrien-Elliott, Mark Foster, Samantha Kersting-Schadek, Agata Gruszczynska, David DeNardo, Todd A Fehniger, Maxim Artyomov, Nathan Singh
Journal: Blood (2023)
Screening for Latent Tuberculosis Infection
Authors: Dick Menzies
Journal: JAMA Network Open (2023)

US Preventive Services Task Force; Carol M. Mangione, MD, MSPH; Michael J. Barry, MD; Wanda K. Nicholson, MD, MPH, MBA; Michael Cabana, MD, MPH; David Chelmow, MD; Tumaini Rucker Coker, MD, MBA; Esa M. Davis, MD, MPH; Katrina E. Donahue, MD, MPH; Carlos Roberto Jaén, MD, PhD, MS; Li Li, MD, PhD, MPH; Gbenga Ogedegbe, MD, MPH; Goutham Rao, MD; John M. Ruiz, PhD; James Stevermer, MD, MSPH; Sandra Millon Underwood, PhD, RN; John B. Wong, MD
Inhibition of ACAA1 Restrains Proliferation and Potentiates the Response to CDK4/6 Inhibitors in Triple-Negative Breast Cancer
Authors: Wen-Ting Peng, Xi Jin, Xiao-En Xu, Yun-Song Yang, Ding Ma, Zhi-Ming Shao, Yi-Zhou Jiang
Journal: Cancer Research (2023)

Abstract Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with unfavorable outcomes. Developing therapeutic targets for TNBC remains a challenge. Here, we identified that acetyl-CoA acyltransferase 1 (ACAA1) is highly expressed in the luminal androgen receptor (LAR) subtype of TNBC compared with adjacent normal tissues in our TNBC proteomics dataset. Inhibition of ACAA1 restrained TNBC proliferation and potentiated the response to the cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor abemaciclib. Mechanistically, ACAA1 interacted with CDK4, and the inhibition of ACAA1 blocked RB transcriptional corepressor 1 (RB1) phosphorylation, resulting in G1–S cell-cycle arrest. Importantly, trimetazidine, a traditional drug for ischemic heart disease, caused a decrease in ACAA1 protein levels and enhanced the efficacy of abemaciclib in preclinical TNBC models. In conclusion, this study identifies that ACAA1 is a therapeutic target in TNBC and suggests the combination of trimetazidine and abemaciclib could be beneficial for ACAA1-high TNBCs. Significance: ACAA1 is highly expressed in TNBC, serving as a potential therapeutic target in ACAA1-high tumors and a predictive biomarker of resistance to CDK4/6 inhibitors for RB1-proficient patients.
Targeting hepatic serine-arginine protein kinase 2 ameliorates alcohol-associated liver disease by alternative splicing control of lipogenesis
Authors: Guannan Li, Hanqing Chen, Feng Shen, Steven Blake Smithson, Gavyn Lee Shealy, Qinggong Ping, Zerong Liang, Jingyan Han, Andrew C. Adams, Yu Li, Dechun Feng, Bin Gao, Masahiro Morita, Xianlin Han, Tim H. Huang, Nicolas Musi, Mengwei Zang
Journal: Hepatology (2023)

Lipid accumulation induced by alcohol consumption is not only an early pathophysiological response but also a prerequisite for the progression of alcohol-associated liver disease (ALD). Alternative splicing regulates gene expression and protein diversity; dysregulation of this process is implicated in human liver diseases. However, how the alternative splicing regulation of lipid metabolism contributes to the pathogenesis of ALD remains undefined.
Medication for Opioid Use Disorder During Pregnancy — Maternal and Infant Network to Understand Outcomes Associated with Use of Medication for Opioid Use Disorder During Pregnancy (MAT-LINK), 2014–2021
Authors: Kathryn Miele, Shin Y. Kim, Rachelle Jones, Juneka H. Rembert, Elisha M. Wachman, Hira Shrestha, Michelle L. Henninger, Teresa M. Kimes, Patrick D. Schneider, Vaseekaran Sivaloganathan, Katherine A. Sward, Vikrant G. Deshmukh, Pilar M. Sanjuan, Jessie R. Maxwell, Neil S. Seligman, Sarah Caveglia, Judette M. Louis, Tanner Wright, Carolyne Cody Bennett, Caitlin Green, Nisha George, Lucas Gosdin, Emmy L. Tran, Dana Meaney-Delman, Suzanne M. Gilboa
Journal: MMWR Surveillance Summaries (2023)

Medication for opioid use disorder (MOUD) is recommended for persons with opioid use disorder (OUD) during pregnancy. However, knowledge gaps exist about best practices for management of OUD during pregnancy and these data are needed to guide clinical care.